Year: 2020
Type: article
Abstract: Canonical inflammasomes are innate immune signaling platforms that are formed in response to intracellular pathogen-associated signals and trigger caspase-1-dependent pyroptosis. Inflammasome formation and signaling is thought to mainly occur in myeloid cells, and in particular monocytes and macrophages. Here we show that small molecule inhibitors of dipeptidyl peptidases 8 and 9 (DPP8/9), which activate the related CARD8 and NLRP1 inflammasomes, also activate pyroptosis in human and rodent resting lymphocytes. We found that both CD4+and CD8+T cells were particularly sensitive to these inhibitors, although the sensitivity of T cells, like macrophages, varied considerably between species. In human T cells, we show that CARD8 mediates DPP8/9 inhibitor-induced pyroptosis. Intriguingly, although activated human T cells express the key proteins known to be required for CARD8-mediated pyroptosis, these cells were completely resistant to DPP8/9 inhibitors. Overall, these data show that resting lymphoid cells can activate at least one inflammasome, revealing additional cell types and states poised to undergo rapid pyroptotic cell death in response to danger-associated signals.
Source: Cell Death and Disease
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,990
Funders: American Association for Cancer Research, Pew Charitable Trusts, Alfred P. Sloan Foundation, Commonwealth Foundation, Entertainment Industry Foundation, Memorial Sloan-Kettering Cancer Center, Robertson Foundation, Pershing Square Sohn Cancer Research Alliance, National Institutes of Health, Stand Up To Cancer, Ludwig Center at Harvard, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases
OpenAlex ID: W3049175993